Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: PLCG1

Gene summary for PLCG1

Gene summary.

Gene information	Species	Human
	Gene symbol	PLCG1
	Gene ID	5335
	Gene name	phospholipase C gamma 1
	Gene Alias	NCKAP3
	Cytomap	20q12
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P19174

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
5335	PLCG1	LZE4T	Human	Esophagus	ESCC	1.34e-05	1.99e-01	0.0811
5335	PLCG1	LZE7T	Human	Esophagus	ESCC	1.39e-07	3.50e-01	0.0667
5335	PLCG1	LZE21D1	Human	Esophagus	HGIN	1.10e-02	2.30e-01	0.0632
5335	PLCG1	LZE22T	Human	Esophagus	ESCC	1.36e-02	2.47e-01	0.068
5335	PLCG1	LZE24T	Human	Esophagus	ESCC	5.86e-11	1.52e-01	0.0596
5335	PLCG1	P1T-E	Human	Esophagus	ESCC	1.92e-05	3.49e-01	0.0875
5335	PLCG1	P2T-E	Human	Esophagus	ESCC	1.28e-14	2.78e-01	0.1177
5335	PLCG1	P4T-E	Human	Esophagus	ESCC	6.27e-10	2.46e-01	0.1323
5335	PLCG1	P5T-E	Human	Esophagus	ESCC	7.83e-09	1.29e-01	0.1327
5335	PLCG1	P8T-E	Human	Esophagus	ESCC	5.08e-12	2.62e-01	0.0889
5335	PLCG1	P9T-E	Human	Esophagus	ESCC	4.66e-08	1.43e-01	0.1131
5335	PLCG1	P10T-E	Human	Esophagus	ESCC	9.08e-29	5.34e-01	0.116
5335	PLCG1	P11T-E	Human	Esophagus	ESCC	2.07e-06	2.89e-01	0.1426
5335	PLCG1	P12T-E	Human	Esophagus	ESCC	3.39e-22	4.29e-01	0.1122
5335	PLCG1	P15T-E	Human	Esophagus	ESCC	7.18e-15	3.28e-01	0.1149
5335	PLCG1	P16T-E	Human	Esophagus	ESCC	1.74e-20	4.14e-01	0.1153
5335	PLCG1	P17T-E	Human	Esophagus	ESCC	2.24e-02	1.24e-01	0.1278
5335	PLCG1	P19T-E	Human	Esophagus	ESCC	1.04e-02	3.12e-01	0.1662
5335	PLCG1	P20T-E	Human	Esophagus	ESCC	2.00e-12	2.69e-01	0.1124
5335	PLCG1	P21T-E	Human	Esophagus	ESCC	5.11e-16	3.55e-01	0.1617

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:005165126	Esophagus	HGIN	maintenance of location in cell	53/2587	214/18723	1.22e-05	3.45e-04	53
GO:005123520	Esophagus	HGIN	maintenance of location	73/2587	327/18723	1.73e-05	4.71e-04	73
GO:000170118	Esophagus	HGIN	in utero embryonic development	77/2587	367/18723	9.56e-05	2.05e-03	77
GO:007084918	Esophagus	HGIN	response to epidermal growth factor	16/2587	49/18723	6.14e-04	8.56e-03	16
GO:007136418	Esophagus	HGIN	cellular response to epidermal growth factor stimulus	15/2587	45/18723	7.05e-04	9.52e-03	15
GO:003812717	Esophagus	HGIN	ERBB signaling pathway	29/2587	121/18723	1.83e-03	1.97e-02	29
GO:000717317	Esophagus	HGIN	epidermal growth factor receptor signaling pathway	25/2587	108/18723	5.87e-03	4.77e-02	25
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:003812718	Esophagus	ESCC	ERBB signaling pathway	82/8552	121/18723	7.23e-07	9.40e-06	82
GO:000717318	Esophagus	ESCC	epidermal growth factor receptor signaling pathway	73/8552	108/18723	3.36e-06	3.73e-05	73
GO:007084919	Esophagus	ESCC	response to epidermal growth factor	38/8552	49/18723	5.24e-06	5.49e-05	38
GO:00066446	Esophagus	ESCC	phospholipid metabolic process	218/8552	383/18723	5.37e-06	5.59e-05	218
GO:007136419	Esophagus	ESCC	cellular response to epidermal growth factor stimulus	35/8552	45/18723	1.11e-05	1.04e-04	35
GO:00066505	Esophagus	ESCC	glycerophospholipid metabolic process	174/8552	306/18723	4.92e-05	3.85e-04	174
GO:0051651111	Esophagus	ESCC	maintenance of location in cell	126/8552	214/18723	6.57e-05	5.00e-04	126
GO:005067318	Esophagus	ESCC	epithelial cell proliferation	238/8552	437/18723	1.19e-04	8.20e-04	238
GO:00507775	Esophagus	ESCC	negative regulation of immune response	112/8552	194/18723	4.67e-04	2.62e-03	112
GO:005067817	Esophagus	ESCC	regulation of epithelial cell proliferation	206/8552	381/18723	5.51e-04	3.02e-03	206
GO:00464864	Esophagus	ESCC	glycerolipid metabolic process	211/8552	392/18723	6.51e-04	3.46e-03	211

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501239	Esophagus	HGIN	Parkinson disease	124/1383	266/8465	5.95e-32	9.70e-30	7.70e-30	124
hsa0517139	Esophagus	HGIN	Coronavirus disease - COVID-19	105/1383	232/8465	7.84e-26	5.11e-24	4.06e-24	105
hsa0502230	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa0513139	Esophagus	HGIN	Shigellosis	71/1383	247/8465	4.89e-07	7.98e-06	6.34e-06	71
hsa0516730	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51
hsa0517029	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51
hsa0541739	Esophagus	HGIN	Lipid and atherosclerosis	51/1383	215/8465	2.95e-03	2.41e-02	1.91e-02	51
hsa0520528	Esophagus	HGIN	Proteoglycans in cancer	47/1383	205/8465	8.23e-03	4.71e-02	3.74e-02	47
hsa05012114	Esophagus	HGIN	Parkinson disease	124/1383	266/8465	5.95e-32	9.70e-30	7.70e-30	124
hsa05171115	Esophagus	HGIN	Coronavirus disease - COVID-19	105/1383	232/8465	7.84e-26	5.11e-24	4.06e-24	105
hsa05022113	Esophagus	HGIN	Pathways of neurodegeneration - multiple diseases	153/1383	476/8465	1.22e-18	4.41e-17	3.50e-17	153
hsa05131114	Esophagus	HGIN	Shigellosis	71/1383	247/8465	4.89e-07	7.98e-06	6.34e-06	71
hsa05167114	Esophagus	HGIN	Kaposi sarcoma-associated herpesvirus infection	51/1383	194/8465	2.46e-04	2.69e-03	2.14e-03	51
hsa05170112	Esophagus	HGIN	Human immunodeficiency virus 1 infection	51/1383	212/8465	2.16e-03	1.90e-02	1.51e-02	51
hsa05417114	Esophagus	HGIN	Lipid and atherosclerosis	51/1383	215/8465	2.95e-03	2.41e-02	1.91e-02	51
hsa05205112	Esophagus	HGIN	Proteoglycans in cancer	47/1383	205/8465	8.23e-03	4.71e-02	3.74e-02	47
hsa05012211	Esophagus	ESCC	Parkinson disease	201/4205	266/8465	1.56e-18	8.72e-17	4.46e-17	201
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

PLCG1

SNV

Missense_Mutation

rs761490511

c.1324N>A

p.Val442Met

p.V442M

P19174

protein_coding

deleterious(0.02)

possibly_damaging(0.904)

TCGA-A7-A26J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PLCG1

SNV

Missense_Mutation

rs200504048

c.2708C>T

p.Ser903Leu

p.S903L

P19174

protein_coding

tolerated(0.12)

benign(0.02)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCG1

SNV

Missense_Mutation

novel

c.1696G>A

p.Glu566Lys

p.E566K

P19174

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PLCG1

SNV

Missense_Mutation

novel

c.653N>A

p.Arg218His

p.R218H

P19174

protein_coding

tolerated(0.43)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PLCG1

SNV

Missense_Mutation

c.2774A>G

p.Lys925Arg

p.K925R

P19174

protein_coding

tolerated(0.25)

possibly_damaging(0.601)

TCGA-AN-A0XN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PLCG1

SNV

Missense_Mutation

c.3358N>A

p.Glu1120Lys

p.E1120K

P19174

protein_coding

deleterious(0.02)

benign(0.201)

TCGA-AO-A12D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

PLCG1

SNV

Missense_Mutation

rs565097087

c.3758N>A

p.Arg1253His

p.R1253H

P19174

protein_coding

tolerated(0.08)

possibly_damaging(0.563)

TCGA-BH-A0EI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PLCG1

SNV

Missense_Mutation

c.1437N>T

p.Met479Ile

p.M479I

P19174

protein_coding

tolerated(0.38)

benign(0)

TCGA-BH-A18U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

PLCG1

SNV

Missense_Mutation

c.2648T>A

p.Ile883Asn

p.I883N

P19174

protein_coding

deleterious(0)

possibly_damaging(0.836)

TCGA-E2-A1II-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

PLCG1

insertion

Frame_Shift_Ins

novel

c.3165_3166insGCAAATCTCCATGCCAAATCTCTAC

p.Thr1056AlafsTer25

p.T1056Afs*25

P19174

protein_coding

TCGA-A8-A090-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		propionic acid derivatives		26398624
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		Pyrazolones		26398624
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		9,10-PHENANTHRENEQUINONE	9,10-PHENANTHRENEQUINONE
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		diclofenac	DICLOFENAC	26398624
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		PHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER	PHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		CEFIXIME	CEFIXIME
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		acetaminophen	ACETAMINOPHEN	26398624
5335	PLCG1	ENZYME, KINASE, PHOSPHOLIPASE, DRUGGABLE GENOME		aspirin	ASPIRIN	26398624

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